MSC2530818
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MedKoo CAT#: 406828

CAS#: 1883423-59-3

Description: MSC2530818 is a Potent, Selective, and Orally Bioavailable CDK8 Inhibitor with CDK8 IC50 = 2.6 nM; Human PK prediction: Cl ~ 0.14 L/H/Kg; t1/2 ~ 2.4h; F > 75%. MSC2530818 displays excellent kinase selectivity, biochemical and cellular potency, microsomal stability, and is orally bioavailable. MSC2530818 demonstrates suitable potency and selectivity to progress into preclinical in vivo efficacy and safety studies.


Chemical Structure

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MSC2530818
CAS# 1883423-59-3

Theoretical Analysis

MedKoo Cat#: 406828
Name: MSC2530818
CAS#: 1883423-59-3
Chemical Formula: C18H17ClN4O
Exact Mass: 340.11
Molecular Weight: 340.811
Elemental Analysis: C, 63.44; H, 5.03; Cl, 10.40; N, 16.44; O, 4.69

Price and Availability

Size Price Availability Quantity
100mg USD 1250
200mg USD 1850
500mg USD 2750
1g USD 3850
2g USD 6850
5g USD 12450
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Synonym: MSC2530818; MSC-2530818; MSC 2530818.

IUPAC/Chemical Name: [(2S)-2-(4-Chlorophenyl)pyrrolidin-1-yl]-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methanone

InChi Key: ODRITQGYYWHQGM-INIZCTEOSA-N

InChi Code: InChI=1S/C18H17ClN4O/c1-11-15-9-13(10-20-17(15)22-21-11)18(24)23-8-2-3-16(23)12-4-6-14(19)7-5-12/h4-7,9-10,16H,2-3,8H2,1H3,(H,20,21,22)/t16-/m0/s1

SMILES Code: O=C(N1[C@H](C2=CC=C(Cl)C=C2)CCC1)C3=CN=C(NN=C4C)C4=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: MSC2530818 is a potent, selective and orally available CDK8 inhibitor with an IC50 of 2.6 nM for CDK8.
In vitro activity: In a commercially available reporter displacement assay, compound 25 (MSC2530818) binds to CDK8 and CDK19 with similar affinity (4 nM), as this study has previously observed across multiple chemotypes. Furthermore, compound 25 demonstrated potent inhibition of WNT-dependent transcription in human cancer cell lines that have constitutively activated WNT signaling. For example, 25 inhibited the reporter-based luciferase readout in several cell lines bearing activating WNT-pathway mutations; LS174T (β-catenin mutant, IC50 = 32 ± 7 nM), COLO205 (APC mutant, IC50 = 9 ± 1 nM) and demonstrated inhibition of WNT3a ligand-dependent reporter readout in PA-1 cells (IC50 = 52 ± 30 nM). Reference: J Med Chem. 2016 Oct 27;59(20):9337-9349. https://pubmed.ncbi.nlm.nih.gov/27490956/
In vivo activity: Compound 25 (MSC2530818) was then assessed in vivo in an established SW620 human colorectal cancer xenograft model in female NCr athymic mice. Tumor-bearing mice were treated orally with compound 25 (50 mg/kg bid or 100 mg/kg qd) for 16 days. Both schedules gave a similar reduction in tumor growth (Figure 6A) with T/C ratios (based on final tumor weights) of 49% and 57%, respectively. Reference: J Med Chem. 2016 Oct 27;59(20):9337-9349. https://pubmed.ncbi.nlm.nih.gov/27490956/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 88.03
DMF:PBS (pH 7.2) (1:1) 0.5 1.47
DMSO 64.3 188.77
Ethanol 39.0 114.43

Preparing Stock Solutions

The following data is based on the product molecular weight 340.81 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. doi: 10.1021/acs.jmedchem.6b00597. Epub 2016 Oct 7. PMID: 27490956.
In vitro protocol: Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. doi: 10.1021/acs.jmedchem.6b00597. Epub 2016 Oct 7. PMID: 27490956.
In vivo protocol: Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. doi: 10.1021/acs.jmedchem.6b00597. Epub 2016 Oct 7. PMID: 27490956.

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1: Czodrowski P, Mallinger A, Wienke D, Esdar C, Poeschke O, Busch M, Rohdich F,
Eccles SA, Ortiz Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D,
Dale TC, Urbahns K, Blagg J, Schiemann K. Structure-based optimization of potent,
selective and orally bioavailable CDK8 inhibitors discovered by high throughput
screening. J Med Chem. 2016 Aug 4. [Epub ahead of print] PubMed PMID: 27490956.